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The federal comparative effectiveness research (CER) initiative is designed to evaluate best practices in health care settings where they can be disseminated for immediate benefit to patients. The CER strategic framework comprises four categories (research, human and scientific capital, data infrastructure, and dissemination) with three crosscutting themes (conditions, patient populations, and types of intervention). The challenge for the field of public health has been accommodating the CER framework within prevention research. Applying a medicine-based, research-to-practice CER approach to public health prevention research has raised concerns regarding definitions of acceptable evidence (an evidence challenge), effective intervention dissemination within heterogeneous communities (a dissemination and implementation challenge), and rewards for best practice at the cost of other promising but high-risk approaches (an innovation challenge). Herein, a dynamic operationalization of the CER framework is described that is compatible with the development, evaluation, and dissemination of innovative public health prevention interventions. An effective HIV, STI, and pregnancy prevention program, It's Your Game…Keep It Real, provides a case study of this application, providing support that the CER framework can compatibly coexist with innovative, community-based public health prevention research.

It’s Your Game…Keep It Real: Can Innovative Public Health Prevention Research Thrive Within a Comparative Effectiveness Research Framework?